Prostaglandins are an extremely important biologically active class of C.sub.20 unsaturated hydroxy acids. They are of widespread occurrence in animal tissues and of varied, extremely potent, biological activities. These acids all have in common the prostanoic acid skeleton, one basic component of which is a five membered cyclopentanone ring.
The therapeutic potential of prostaglandins and the current lack of an abundant natural source of these compounds have led to a number of laboratory investigations to provide a total synthesis as a method of obtaining them. Obviously, a fundamentally important starting material for development of a basic prostaglandin synthesis is the cylopentanone ring, since it is basic to the prostanoic acid skeletal structure.
The cyclization of 4-pentenal to cyclopentanone by chloro tris-(triphenylphosphine) rhodium(I) is known. See for example, Sakai, K.; Ide, J.; Oda, O.; Nakamura, N. Tetrahedron Lett. 1972, 1287-1290, and Lochow, C. F.; Miller, R. G. J. Am. Chem. Soc. 1976, 98, 1281-1283, which are incorporated herein by reference. However, this reaction has not been achieved at sufficiently high yields to make it an attractive and realistic starting point for prostaglandin synthesis.
In the Sakai et al. reference previously mentioned herein, the catalyst employed in Wilkinson's Catalyst, that is tris(triphenylphosphine) chlororhodium of the formula: EQU RhCl(PPh.sub.3).sub.3
However, the yield of cyclopentanone from his intramolecular cyclization of 4-pentenal, with Wilkinson's Catalyst is only 17%, and the reaction requires equivalent amounts of the rhodium complex (i.e. it is not catalytic).
It has now been discovered that with the aid of certain newly developed rhodium catalysts, this basic reaction can be conducted under mild conditions to provide high yields of the desired cyclopentanone. This is the primary object of the invention. The method of accomplishing this object, as well as others, will be apparent from the detailed description, which follows.